Based on the observations that DR6 knockout reduced BBB functional protein glucose transporter 1 (Glut-1) and caused BBB leakage in mice and zebrafish [7], we hypothesised that BEC DR6 may play a protective role in maintaining BBB integrity and function in the presence of Aβ; while impairments of BEC DR6 can occur during AD pathogenesis. This evidence concerns the gene TNFRSF21 and Alzheimer disease.